1. Field of the Invention
The present invention relates to a compound having an aldose reductase inhibitory activity and more specifically to a tetrazoleacetic acid derivative and an aldose reductase inhibitor which comprises the tetrazoleacetic acid derivative as an effective component and which is effective as a preventive medicine and/or remedy for diabetic complications as well as a method for alleviating or reducing diabetic complications.
2. Prior Art
It has been known that aldose reductase inhibitors are effective for prevention and/or treatment of diabetic copmplications. This is detailed in the article of Dr. Tsuyoshi TANIMOTO [Division of Biological Chemistry and Reference Standards, National Institute of Hygienic Sciences] (see Farumashia, 1988,24, No. 5, pp. 459-463). This article discloses the chemical structures and 50% inhibitory concentrations (IC.sub.5 0) of representative aldose reductase inhibitors such as Alrestatin, Tolrestat, 4-Isopropyl-BFOC, Sorbinil, M-79175, Alconil, ADN-138, Epalrestat, CT-112 and Statil.
The inventors of this invention already conducted screening of novel aldose reductase inhibitors, found that compounds represented by the following general formula (III): ##STR2## [in Formula (III), R.sub.1 represents a hydrogen atom or a group: --A--COOR.sub.5 (wherein A represents an alkylene group having 1-4 carbon atoms and R.sub.5 represents a hydrogen atom or a lower alkyl group) and R.sub.2, R.sub.3 and R.sub.4 may be the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group, an alkoxy group, a phenyl group, a phenoxy group, a nitro group, a residue represented by the formula: NHCOCOOR.sub.6 (wherein R.sub.6 represents a hydrogen atom or a lower alkyl group) or a residue represented by the following formula: ##STR3## wherein A and R.sub.5 are the same as those defined above)] have very high aldose reductase inhibitory activity and already filed a patent application (Japanese Patent Application Serial No. Hei 1-70520).
Among these chemical substances according to the present invention, [5-(2-thienyl)tetrazol-1-yl] acetic acid and ethyl ester thereof as well as [5-(2-furyl)tetrazol-1-yl] acetic acid and ethyl ester thereof are reported in an article of A. K. Zorenzen, Acta Chem. Scand., 1972, 26, p. 541. However, this article only discloses a method for preparing these substances, but there is no disclosure about the biological activity thereof.